Combinatorial chemopreventive effect of Azadirachta indica and Ocimum sanctum on oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis in a rat forestomach carcinogenesis model.
BACKGROUND
We investigated the combinatorial chemopreventive efficacy of Azadirachta indica (AI) and Ocimum sanctum (OS) against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis, based on changes in oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis.


METHODS
Male Wistar rats were assigned to four groups. Rats in groups 1 and 2 received MNNG (150 mg/kg body weight i.g.) three times with a gap of two weeks in between the treatment. Group 2 rats additionally received ethanolic AI (100 mg/kg body weight i.g.) and OS (150 mg/kg body weight i.g.) leaf extract three times per week for 26 weeks. Group 3 animals were given AI and OS leaf extract alone, whereas group 4 served as the control.


RESULTS
Lipid and protein oxidation and status of the antioxidants, superoxide dismutases, catalase, reduced glutathione (GSH) and GSH-dependent enzymes together with markers of proliferation (proliferating cell nuclear antigen [PCNA], glutathione S-transferase-Pi [GST-P]), invasion (cytokeratin [CK]), angiogenesis (vascular endothelial growth factor [VEGF]) and apoptosis (Bcl-2, Bax, cytochrome C and caspase-3) were used to biomonitor chemoprevention. Rats administered MNNG developed forestomach carcinomas that displayed low lipid and protein oxidation coupled to enhanced antioxidant activities, and overexpression of PCNA, GST-P, CK, VEGF and Bcl-2 with downregulation of Bax, cytochrome C and caspase-3. Coadministration of AI and OS extract suppressed MNNG-induced gastric carcinomas accompanied by modulation of the oxidant-antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis.


CONCLUSIONS
The results of the present study suggest that chemoprevention by AI and OS combination may be mediated by their antioxidant, antiangiogenic, antiproliferative and apoptosis inducing properties.
Manikandan
P
P
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.
Vidjaya Letchoumy
P
P
Prathiba
D
D
Nagini
S
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D031601:Azadirachta; D004195:Disease Models, Animal; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009389:Neovascularization, Pathologic; D031339:Ocimum / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000975:Antioxidants; D016877:Oxidants; D010936:Plant Extracts; D008769:Methylnitronitrosoguanidine